A GPCR is a transmembrane receptor that receives a specific extracellular ligand as a stimulus, transmits the signal to and activates the intracellular G protein. GPCR has a characteristic structure that it penetrates the cell membrane seven times. Upon being bound by a specific ligand, GPCR greatly changes in its structure and thereby activates the G protein.
Among G protein-coupled receptors (GPCR) that binds a fatty acid as a ligand are GPR120 and GPR40 and their analogous molecules, and GPR41 and GPR42 as analogous molecules of GPR40.
A fatty acid receptor GPR120 exists in the intestinal tract, lung, brain, etc., specifically in the intestinal tract, and is known to have 95% identity in amino acid sequence with a G protein-coupled 14273 receptor. It is known that the cells expressing GPR120 in intestinal tract release intestinal hormone peptides, such as glucagon-like peptide (GLP-1) and cholecystokinin (CCK), when it is treated with a fatty acid which functions as an activating ligand of GPR120.
GLUCKSMANN, M. Alexandra, et al. first described 14273 receptor as a novel GPCR, and reported a method for identifying agonists and antagonists by using this GPCR (WO00/00611, WO00/50596).
Further, GIMENO, Ruth et al. reported a method for identifying nucleic acid molecules and polypeptides that are involved in metabolic diseases, and a method for identifying compounds for metabolic diseases that are characterized by the activity of 14273 polypeptide. They also reported that the 14273 receptor could be used for diagnosis, prevention, or treatment of metabolic diseases such as obesity, cibophobia, hyperphagia and diabetes (WO02/067868).
These peptides control the physiological functions involved in feeding. For example, they control the secretion of insulin from pancreatic β cells, the secretion of pancreatic fluid from pancreas, the secretion of bile from gallbladder, and the appetite suppression in the central nervous system. Therefore, an administration of the substance that activates the function of GPR120 to an organisms would be useful for preventing and/or treating diabetes by accelerating the secretion of insulin, for treating incompetent digestive function by promoting the secretion of digestive juice, and for preventing and/or treating obesity by suppressing appetite. Moreover, these peptides are involved in maintenance of nerve cells in the central nervous system. GPR120 exists not only in intestinal tract but also in lung, pituitary gland, adipocyte and tongue, and they play important roles in each organ. They are considered to be involved in secretion of pituitary hormone in pituitary gland, decomposition of fat in adipocyte, gustatory sense in tongue, and lung cell protection in lung.
The present inventors previously analyzed the function of a polypeptide derived from a GPCR gene GT01 (GPR120) and carried out intensive researches to identify compounds that act on the peptide. They unexpectedly found that GT01 polypeptide is distributed on the surface of secreting cells in the human intestine and it has a function of accelerating the secretion of CCK, which functions in feeding control, and identified the compounds which function as the ligand for GT01 polypeptide. More specifically, the present inventors have proposed the compounds for the pharmaceutical composition for treating feeding disorders, and as examples of such compounds, free fatty acids such as capric acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, stearic acid, arachic acid, behenic acid, margaric acid, palmitoleic acid, eicosatrienoinic acid, elaidic acid, petroselinic acid, oleinic acid, linolenic acid, γ-linolenic acid, homo-γ-linolenic acid, arachidonic acid, eicosadienoic acid, eicosatrienoic acid, eicosapentanoic acid, docosahexanoic acid, linolic acid, eicosatetraenoic acid, and vaccenic acid (Japanese Patent Laid-open No. 2005-15358).
GPR40 was found in 1997 as an orphan receptor whose ligand was unknown. Later researches revealed that the receptor is expressed in pancreas and its ligand is a fatty acid, and that free fatty acids such as oleic acid and linolenic acid act on GPR40 to promote secretion of insulin from pancreatic β cells. Therefore, it is expected that a compound that acts on GPR40 will function as a preventive or therapeutic drug for diabetes through a novel action mechanism (WO03/068959A1).
On the other hand, Miyata and Suzuki reported that the following compounds have an activity as ligands for PPARγ (Bioorganic & Medicinal Chemistry Letters (2005), 15(6), 1547-1551).

However, PPARγ is an intranuclear receptor and is basically different from GPCR.
Miyata and Suzuki also reported that the following compound has an activity as ligands for PPARα (Bioorganic & Medicinal Chemistry Letters (2006), 16(12), 3249-3254).

However, PPARα is an intranuclear receptor and is basically different from GPCR.
The following compound (GW9508) is known as an agonist compound for GPR40 and GPR120 (Br J Pharmacol. 2006 July; 148(5) 619-628).
